Dextran‐induced Lowering of Parameters of the Kallikrein‐kinin System in Rat Plasma: Significance of Monoamine‐depleting Agents

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Activation of plasminogen‐free rat citrated plasma (RCPL‐P) with acetone/kaolin yielded BAEe‐esterase activities of 0.6‐0.8 U/ml. Gel filtration demonstrated one single peak of BAEe‐esterase activity (mol. wt. approximately 135000) with a kininogenase‐esterase ratio (3.3) close to that known for human plasma kallikrein (2.7). Similarly activated rat citrated plasma (RCPL) revealed on gel filtration an additional esterase peak (mol. wt. approximately 47,000) with a low kininogenase‐esterase ratio (0.3), and should accordingly not be used for a BAEe‐esterase assay of rat plasma kallikrein. Acetone activation of RCPL‐P and of RCPL yielded prekallikrein activator (PKA) activities which were about doubled by treatment with kaolin to 1.9‐2.1 and 3.5‐4.2 PKA‐U/ml respectively. Gel filtration of acetone‐activated RCPL‐P or RCPL revealed two peaks of PKA activity, mol. wt. approximately 110,000 corresponding to activated factor XII (XIIa), and mol. wt. approximately 33,000 corresponding to XII fragments (XIIf). Kaolin‐treatment of acetone‐activated RCPL‐P, but not of RCPL, caused an extensive fragmentation of XII, to the 4‐6 times more active XIIf. The lower yield of PKA‐activity in acetone/kaolin‐activated RCPL‐P, as compared with activated RCPL, seems to be due to the absence of a factor of significance for the activation of factor XII, which is not plasmin, plasma kallikrein, or high molecular weight kininogen.

Section: Baee-esterase In Acetone-and Kaolin-activated Rcpl and Rcpl-pmentioning

confidence: 69%

Section: Prekallikrein Activator In Acetone-and Kaolin-activated Rcplmentioning

confidence: 99%

mentioning

confidence: 99%

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Prekallikrein Activator and Kallikrein in Acetone‐ and Kaolin‐activated Rat Plasma

Berstad

1979

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“…The observed lowering by dextran of plasminogen proactivator, pro-PGA, (Berstad & Briseid 1982) was accordingly to be expected. More surprising, however, was the fact that EACA or AMCHA did not cause any detectable inhibition of the lowering of PG caused by dextran (Briseid et al 1979) or serotonin (Berstad 1980a), nor did recent in vitro experiments reveal an inhibition by AMCHA of the PGA activity developed by acetone treatment of rat plasma (Berstad & Briseid 1982). On the other hand, AMCHA alone was found to cause a clear lowering of the capacity ofHMWK to function as a cofactor in the activation of factor XI1 (Briseid et a/.…”

Section: Discussionmentioning

confidence: 96%

“…Dextran injected intravenously into rats was previously found to cause some reduction of the level of plasminogen (PG) in plasma (Briseid et a/. 1979;Berstad 1980a), an effect probably mediated through a release of serotonin from mast cells (Berstad 1980a & b).…”

Section: Discussionmentioning

confidence: 99%

The Initial Phase of the Dextran‐induced Anaphylactoid Reaction in the Rat: A Comparison of Inhibitors of the Blood Pressure Fall

Berstad

1982

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The histamine H2‐receptor antagonist cimetidine (25–100 mg/kg) caused a partial inhibition of the pronounced blood pressure fall induced by dextran (Macrodexå, 40–100 mg/kg) in the rat. The inhibition by cimetidine could not be distinguished from the inhibition achieved by the serotonin D‐receptor antagonist bromolysergic acid diethylamide (BOL, 1–4 mg/kg). Doses of cimetidine and BOL that gave submaximum inhibitory effects separately, showed approximately additive effects when combined. The combined effect of these drugs never exceeded the maximum effects of the drugs separately, whereas injection of tranexamic acid (AMCHA, 100–300 mg/kg) together with cimetidine or BOL, increased the total inhibition. Previous works showed that dextran injected intravenously into rats reduced the level of plasminogen (PG) and plasminogen proactivator (pro‐PGA) in plasma (Briseid et al. 1979; Berstad 1980a; Berstad & Briseid 1982). High doses of AMCHA (200 mg/kg) did not inhibit these effects, but significantly increased the lowering caused by dextran of the capacity of high molecular weight kininogen (HMWK) to function as a cofactor in the activation of factor XII. BOL (1–4 mg/kg, Berstad 1981) and cimetidine (50–100 mg/kg) also reduced the cofactor capacity of HMWK in the doses that were required to provide a manifest inhibition of the dextran‐induced blood pressure fall. It is suggested that the early phase of the state of shock induced by dextran in the rat can be counteracted at different sites, correlated with histamine and serotonin receptors on the one hand, and with an effect antagonized by AMCHA, on the other. The lowest effective doses of cimetidine and BOL were rather high, suggesting a less specific mechanism for their effects than inhibition at selective receptor sites.

Activation of Factor XII in Plasma from Rats Pretreated with Tranexamic Acid. Inhibition of a Plasmin‐induced Loss of the Functional Activity of High Molecular Weight Kininogen

Briseid

Ryssdal

1980

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Incubation of plasma from rats pretreated with tranexamic acid (40 mg/l 00 g) with acetone (23 % v/v) yielded enzyme preparations in which all the plasminogen present was recovered as plasmin and a plasmin‐like substance without affinity for lysine‐Sepharose. This substance, designated “plasmin”, was separated from plasmin and kallikrein in a three‐step procedure using columns of lysine‐Sepharose, DEAE‐Sephadex A‐50, and arginine‐Sepharose. The ratios of fibrinolytic, caseinolytic, LEe esterase, BAEe esterase and kininogenase activities of “plasmin” corresponded well with those of rat plasmin and human plasmin. Both rat plasmin and “plasmin” destroyed the capacity of high molecular weight kininogen (HMWK) to function as a cofactor in the activation of factor XII in rat plasma, without causing a corresponding release of the kinin part of the molecule. Rat plasma kallikrein induced full release of kinin from HMWK, but the functional capacity was retained. It is suggested that the reduced extent of activation of factor XII observed in plasma from rats injected intravenously with dextran, or rat plasma that has been passed through a column with lysine‐Sepharose, is due to the loss of functional HMWK caused by plasmin activated in vivo or on the column.